The study assessed the relationship between the anticholinergic activity of imipramine, specifically changes in cardiac vagal control, and improvement in the symptoms of anxiety following treatment of generalized anxiety disorder patients with imipramine. Its purpose was to replicate previous findings from this laboratory relating anxiety reduction and cardiac vagal control and to extend those findings to include assessment of imipramine blood levels, desipramine blood levels, and anticholiriergic activity resulting from the imipramine. Fourteen patients with generalized anxiety disorder were treated for six weeks with a flexible dose regimen of imipramine. Cardiac vagal tone, measured as respiratory sinus arrythmia, and ratings from several anxiety-assessment instruments were assessed before and after treatment. During the last week of treatment, blood samples were drawn and blood levels of imipramine and desipramine were determined. The anticholinergic activity of imipramine was also determined from these blood samples. The following results were obtained: Decrease in ratings of anxiety were greatest in patients who showed the smallest decreases in cardiac vagal tone. Thus, the initial purpose of the study was achieved: our earlier findings were replicated. Similar relationships were found between anxiety reduction and both desipramine and anticholinergic levels. There was no relationship between anxiety reduction and blood imipramine levels. The strongest finding consisted of the inverse relationship between blood desipramine levels and decreases in anxiety levels following treatment (r = .82; p < .001). That is, the greater the desipramine levels were at the end of treatment, the smaller was the reduction in anxiety. Further analyses are currently underway. Results of these analyses as well as interpretation of results will follow.